Fungal infection has become the leading cause for high morbidity and mortality in immunodeficient patients. During the past 20 years, the incidence of fungal infection increased significantly. People at high-risk of fungal infections includes critical patients, surgical patients and those patients suffering from HIV infection, leukemia and other tumors. Patients with organ transplant are also at high risk of fungal infection.
Echinocandins, as a new class of antifungal agents, exhibit good effects in the treatment of infections caused by Candida or Aspergillus. Caspofungin and Micafungin are the representatives of such medicaments. Echinocandins inhibit fungus by suppressing the formation of 1,3-β glycosidic bond, so as to reduce the harm to human body, and reduce the side effects while remaining high efficiency. Therefore, they are safer in use than traditional antifungal agents.
FK463 (sodium Micafungin) is the compound of formula II (R is a sodium ion), which is developed by Japan Fujisawa Toyama Co., Ltd, Takaoka Plant under the trade name Mycamine, and currently sold in several countries as antifungal agent for intravenous administration. It is obtained by cutting the side-chain of FR901379 as precursor (compound of Formula III, R is a sodium ion or a hydrogen ion) by enzyme, thus forming FR179642 (compound of Formula I, R is a hydrogen or a sodium ion) (see U.S. Pat. No. 5,376,634, EP0431350 and Chinese patent CN1161462C for specific methods), and then chemically modifying FR179642 (see Patent Publication WO9611210, WO9857923, WO2004014879 for specific preparation and purification methods).

Specific scheme is shown as follows:

As well-known in the art, crystals are generally more stable than the amorphous state. Therefore, the present inventors want to find a suitable crystal of compound of formula I as drug intermediate, so that the compound of formula I is more stable during the storage.
Compound of formula I is difficult to be crystallized, and usually amorphous state. With respect to the final use in the treatment or as an intermediate of compound of formula II, it is desirable to obtain crystals with good stability and high purity.
Several crystals with good stability and suitable for transportation and storage are obtained by the method of the present invention, and the yield during the preparation is high.